2puq
From Proteopedia
| Line 1: | Line 1: | ||
| - | [[Image:2puq.gif|left|200px]] | + | [[Image:2puq.gif|left|200px]] |
| - | + | ||
| - | '''Crystal structure of active site inhibited coagulation factor VIIA in complex with soluble tissue factor''' | + | {{Structure |
| + | |PDB= 2puq |SIZE=350|CAPTION= <scene name='initialview01'>2puq</scene>, resolution 2.050Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=GLC:GLUCOSE'>GLC</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene> and <scene name='pdbligand=CH2:METHYLENE GROUP'>CH2</scene> | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/Coagulation_factor_VIIa Coagulation factor VIIa], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.21 3.4.21.21] | ||
| + | |GENE= F7 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), ACE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | }} | ||
| + | |||
| + | '''Crystal structure of active site inhibited coagulation factor VIIA in complex with soluble tissue factor''' | ||
| + | |||
==Overview== | ==Overview== | ||
| Line 10: | Line 19: | ||
==About this Structure== | ==About this Structure== | ||
| - | 2PUQ is a [ | + | 2PUQ is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry 2PMM. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PUQ OCA]. |
==Reference== | ==Reference== | ||
| - | Engineering the substrate and inhibitor specificities of human coagulation Factor VIIa., Larsen KS, Ostergaard H, Bjelke JR, Olsen OH, Rasmussen HB, Christensen L, Kragelund BB, Stennicke HR, Biochem J. 2007 Aug 1;405(3):429-38. PMID:[http:// | + | Engineering the substrate and inhibitor specificities of human coagulation Factor VIIa., Larsen KS, Ostergaard H, Bjelke JR, Olsen OH, Rasmussen HB, Christensen L, Kragelund BB, Stennicke HR, Biochem J. 2007 Aug 1;405(3):429-38. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17456045 17456045] |
[[Category: Coagulation factor VIIa]] | [[Category: Coagulation factor VIIa]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| Line 25: | Line 34: | ||
[[Category: active site inhibitor; substrate profile]] | [[Category: active site inhibitor; substrate profile]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:17:37 2008'' |
Revision as of 16:17, 20 March 2008
| |||||||
| , resolution 2.050Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , and | ||||||
| Gene: | F7 (Homo sapiens), ACE (Homo sapiens) | ||||||
| Activity: | Coagulation factor VIIa, with EC number 3.4.21.21 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of active site inhibited coagulation factor VIIA in complex with soluble tissue factor
Contents |
Overview
The remarkably high specificity of the coagulation proteases towards macromolecular substrates is provided by numerous interactions involving the catalytic groove and remote exosites. For FVIIa [activated FVII (Factor VII)], the principal initiator of coagulation via the extrinsic pathway, several exosites have been identified, whereas only little is known about the specificity dictated by the active-site architecture. In the present study, we have profiled the primary P4-P1 substrate specificity of FVIIa using positional scanning substrate combinatorial libraries and evaluated the role of the selective active site in defining specificity. Being a trypsin-like serine protease, FVIIa had P1 specificity exclusively towards arginine and lysine residues. In the S2 pocket, threonine, leucine, phenylalanine and valine residues were the most preferred amino acids. Both S3 and S4 appeared to be rather promiscuous, however, with some preference for aromatic amino acids at both positions. Interestingly, a significant degree of interdependence between the S3 and S4 was observed and, as a consequence, the optimal substrate for FVIIa could not be derived directly from a subsite-directed specificity screen. To evaluate the role of the active-site residues in defining specificity, a series of mutants of FVIIa were prepared at position 239 (position 99 in chymotrypsin), which is considered to be one of the most important residues for determining P2 specificity of the trypsin family members. This was confirmed for FVIIa by marked changes in primary substrate specificity and decreased rates of antithrombin III inhibition. Interestingly, these changes do not necessarily coincide with an altered ability to activate Factor X, demonstrating that inhibitor and macromolecular substrate selectivity may be engineered separately.
Disease
Known diseases associated with this structure: Esophageal squamous cell carcinoma OMIM:[606551], Factor VII deficiency OMIM:[227500], Myocardial infarction, decreased susceptibility to OMIM:[227500]
About this Structure
2PUQ is a Protein complex structure of sequences from Homo sapiens. This structure supersedes the now removed PDB entry 2PMM. Full crystallographic information is available from OCA.
Reference
Engineering the substrate and inhibitor specificities of human coagulation Factor VIIa., Larsen KS, Ostergaard H, Bjelke JR, Olsen OH, Rasmussen HB, Christensen L, Kragelund BB, Stennicke HR, Biochem J. 2007 Aug 1;405(3):429-38. PMID:17456045
Page seeded by OCA on Thu Mar 20 18:17:37 2008
